Accelerating Transdisciplinary Epidemiology of Colorectal Cancer Summary Tumor evolution is a heterogeneous process influenced by somatic molecular alterations, host immunity, diet, lifestyle, microbiota, and environment. Thus, I plan to take a transdisciplinary approach integrating molecular- level research, population-level study design, and assessment of environment, diet and lifestyle, utilizing my unique interdisciplinary expertise. I have been developing the transdisciplinary field of Molecular Pathological Epidemiology (MPE) with integrated strengths of both pathology and epidemiology. I will pursue two interconnecting synergistic Themes: (1) MPE of colorectal cancer (CRC) and (2) accelerating transdisciplinary epidemiology. In Theme 1, I will integrate tumor molecular and immunity analyses in 2,500 CRCs in the Nurses' Health Study (NHS), the NHS2 and the Health Professionals Follow-up Study (HPFS). I have successfully built an unprecedented high-dimensional CRC database on long-term exposures, tumor pathology, microbial, molecular and immunity data, and clinical outcome, to test the following broad-term hypotheses: (1.1) Dietary, lifestyle, environmental and genetic factors influence CRC incidence differentially by molecular, microbial and immunity subtypes. (1.2) CRC molecular features influence immune response to CRC. (1.3) CRC molecular and immunity status influences patient survival and response to drugs or modifiable dietary, lifestyle or environmental factors. (1.4) The degree of CRC intratumor heterogeneity is associated with worse prognosis and specific epidemiologic, clinical, and pathological features. We will extend our integrative research to various other settings to replicate findings and assess potential effect modifications by ethnic, socioeconomic and other factors. This project may identify potential strategies to target molecular alterations, immunity and microbiota for CRC prevention and therapy. My Theme 2 plans are; (2.1) to develop research frameworks, analysis designs and statistical methods, to address molecular and etiologic heterogeneity of cancer; (2.2) to grow the ongoing International MPE Meeting Series, to facilitate seamless transdisciplinary integration with a goal of making the STROBE-MPE guidelines; and (2.3) to synergize with experts and build new integrative transdisciplinary models, causal inference-MPE and MPE-health communication research. Thus, I aim to promote transdisciplinary integration of molecular pathology and population cancer science, and to address a critical unmet need to integrate analyses of cancer immunity, tumor molecular profiles (including microbiota and intratumor heterogeneity), modifiable exposures, genetics, and CRC incidence and death. I also try to address challenges in transdisciplinary epidemiology, including paucity of interdisciplinary experts and training programs, as well as lack of research guidelines in MPE. My unique qualifications and transdisciplinary research program can not only provide new insights on CRC etiologies in a population-based scale, but also develop novel methods / frameworks, and frontiers of population cancer science. As such, my proposed research will likely have major impacts on future research, clinical practice and public health.

Public Health Relevance

I plan to conduct Molecular Pathological Epidemiology (MPE) research on colorectal cancer (CRC) tumor characteristics, to gain insights into the role of environmental, diet, lifestyle, medical, screening and genetic factors in CRC incidence, mortality and clinical outcome. I will primarily utilize the resources of the Nurses' Health Study (NHS), the Nurses' Health Study II (NHS2), and the Health Professionals Follow-up Study (HPFS). I will also accelerate the field of transdisciplinary epidemiology with the goal of advancing several fronts of population cancer sciences to reduce suffering and death from cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA197735-06
Application #
10020904
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Lam, Tram K
Project Start
2019-08-01
Project End
2022-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Liu, Po-Hong; Wu, Kana; Ng, Kimmie et al. (2018) Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women. JAMA Oncol :
Kosumi, Keisuke; Mima, Kosuke; Baba, Hideo et al. (2018) Dysbiosis of the gut microbiota and colorectal cancer: the key target of molecular pathological epidemiology. J Lab Precis Med 3:
Neumeyer, Sonja; Banbury, Barbara L; Arndt, Volker et al. (2018) Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. Br J Cancer 118:1639-1647
Ogino, Shuji; Giannakis, Marios (2018) Immunoscore for (colorectal) cancer precision medicine. Lancet 391:2084-2086
He, Xiaosheng; Wu, Kana; Ogino, Shuji et al. (2018) Association Between Risk Factors for Colorectal Cancer and Risk of Serrated Polyps and Conventional Adenomas. Gastroenterology 155:355-373.e18
Van Blarigan, Erin L; Fuchs, Charles S; Niedzwiecki, Donna et al. (2018) Marine ?-3 Polyunsaturated Fatty Acid and Fish Intake after Colon Cancer Diagnosis and Survival: CALGB 89803 (Alliance). Cancer Epidemiol Biomarkers Prev 27:438-445
Hu, Yang; Ding, Ming; Yuan, Chen et al. (2018) Association Between Coffee Intake After Diagnosis of Colorectal Cancer and Reduced Mortality. Gastroenterology 154:916-926.e9
Cao, Yin; Wu, Kana; Mehta, Raaj et al. (2018) Long-term use of antibiotics and risk of colorectal adenoma. Gut 67:672-678
Ogino, Shuji; Nowak, Jonathan A; Hamada, Tsuyoshi et al. (2018) Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine. Gut 67:1168-1180
Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K et al. (2018) Genetic Mechanisms of Immune Evasion in Colorectal Cancer. Cancer Discov 8:730-749

Showing the most recent 10 out of 109 publications